title: Increased expression of estrogen receptor α-36 by breast cancer oncogene IKKε promotes growth of ER-negative breast cancer cells.
abstract: OBJECTIVE
  The expression of estrogen receptor-α (ERα) is one of the most important diagnostic and prognostic factors of breast cancer. Recently, ERα-36 has been identified as a novel variant of ER-α. ERα-36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. The noncanonical IKK family member IKKε is essential for regulating antiviral signaling pathways and is recently discovered as a breast cancer oncogene. IKKε interacts with and phosphorylates ERα on serine 167, induces ERα transactivation activity and enhances ERα binding to DNA in ER-positive breast cancer cells. However, the correlation between IKKε and the ERα-36 signaling pathway in ER-negative breast cancer cells remains unclear.
  
  
  RESULTS
  In this study, we show that IKKε interacts with ERα-36 and increases its expression in breast cancer cells. As shown by western blot assays, the upregulation of ERα-36 by IKKε was significant. In MDA-MB-231 cells which are ER-negative, IKKε was able to increase the expression of ERα-36 in a dose-dependent manner, and the RNA interference assay indicated the correlation between IKKε and ERα-36 expression. Moreover, IKKε enhanced the growth of MDA-MB-231 and MDA-MB-436 cells.
  
  
  CONCLUSIONS
  These results suggest that IKKε increases ERα-36 expression and is involved in ERα-36 mediated non-genomic estrogen signaling.
authors.affiliation: School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Li
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.forename: Jingcai
authors.initials: J
authors.lastname: Zou
authors.forename: Cheng
authors.initials: C
authors.lastname: Ge
authors.forename: Kaitao
authors.initials: K
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering; D051550:I-kappa B Kinase